JP2005511725A5 - - Google Patents

Description

Each formulation was applied to the dorsal skin of an anesthetized rat, approximately 4 cm ² area marked with an indelible felt tip marker. Approximately 30 mg of the formulation (containing 0.17 μg E or EP) was applied to the site with a curved glass rod applicator. The formulation “disappeared” by the time it was apparently absorbed into the skin. It took 5-10 minutes. During this procedure, no consistent changes were observed in the formulation. The amount of formulation applied and the area of application site were important for each animal.

Claims (10)

Comprising an effective skin permeation amount of one or more phosphate derivatives of one or more pharmaceutical hydroxy compounds and a carrier,
The carrier comprises a complex of tocopheryl phosphate and a complexing agent, and the complexing agent comprises arginine, lysine, histazine, and the following formula:
NR ¹ R ² R ³
(Where
R ¹ is selected from the group comprising C6-C22 alkyl groups mixed with straight or branched chains and carbonyl derivatives thereof;
R ² and R ³ are independently H, CH ₂ COOX, CH ₂ CHOHCH ₂ SO ₃ X, CH ₂ CHOHCH ₂ OPO ₃ X, CH ₂ CH ₂ COOX, CH ₂ COOX, CH ₂ CH ₂ CHOHCH ₂ SO ₃ X or CH ₂ CH ₂ CHOHCH ₂ OPO ₃ X selected from the group consisting of H, Na, K, or alkanolamine when R ² and R ³ are not both H;
When R ¹ is RCO, R ² is CH ₃ and R ³ is (CH ₂ CH ₂ ) N (C ₂ H ₄ OH) —H ₂ CHOPO ₃ , or R ² and R ³ are taken together. Te _{N (CH 2) 2 N (} C 2 H 4 OH) is CH 2 COO-)
A topical skin preparation selected from the group consisting of: The topical skin preparation of claim 1 , wherein the pharmaceutical hydroxy compound is selected from the group consisting of estrogen, estradiol, testosterone, atropine, morphine and mixtures thereof. The phosphoric acid derivative is a free phosphoric acid; a salt thereof; a phosphate ester having two molecules of a pharmaceutical hydroxy compound; a phosphatidyl compound in which the oxygen of the free phosphoric acid forms a bond with an alkyl group or a substituted alkyl group; Or present in a form selected from the group consisting of amphoteric surfactants, cationic surfactants and one or more complexing agents selected from the group consisting of amino acids having nitrogen functional groups; and mixtures thereof The topical skin preparation according to claim 1 or 2 . Phosphoric acid derivatives of the pharmaceutical hydroxy compound is estrogen phosphate ester, estradiol phosphate ester, testosterone phosphate ester, atropine phosphate ester, is selected from morphine phosphate ester and mixtures thereof, according to claim 3 Topical skin preparation. The phosphoric acid derivative is an amphoteric surfactant, to form one or more complexing agents and complexes selected from the group consisting of amino acids with cationic surfactant and nitrogen functional groups, according to claim 3 Topical skin formulation. The complexing agent is arginine, lysine, histadine and the following formula:
NR ¹ R ² R ³
(Where
R ¹ is selected from the group comprising C6-C22 alkyl groups mixed with straight or branched chains and carbonyl derivatives thereof;
R ² and R ³ are independently H, CH ₂ COOX, CH ₂ CHOHCH ₂ SO ₃ X, CH ₂ CHOHCH ₂ OPO ₃ X, CH ₂ CH ₂ COOX, CH ₂ COOX, CH ₂ CH ₂ CHOHCH ₂ SO ₃ X or CH ₂ CH ₂ CHOHCH ₂ OPO ₃ X, and X is H, Na, K or alkanolamine when R ² and R ³ are not H;
And where R ¹ is RCO, R ² can be CH ₃ and R ³ is (CH ₂ CH ₂ ) N (C ₂ H ₄ OH) —H ₂ CHOPO ₃ or R ² and R ³ together _{N (CH 2) 2 N (} C 2 H 4 OH) may be CH 2 COO-)
The topical skin preparation according to claim 5 , selected from the group consisting of: The complexing agent is a complex with a phosphate derivative of a pharmaceutical hydroxy compound selected from the group consisting of estrogen phosphate ester, estradiol phosphate ester, testosterone phosphate ester, atropine phosphate ester, morphine phosphate ester and mixtures thereof. The topical skin preparation according to claim 6 , wherein   The topical skin preparation of claim 1, wherein the carrier comprises tocopheryl phosphate lauryliminodipropionate. The carrier is 61.95% deionized water, 5.00% glycerin, 0.05% trisodium EDTA, 0.50% carbomer, 7.50% tocopheryl phosphate lauryliminodipropionate. 2.00% cetearyl alcohol and ceteareth-20, 1.00% glyceryl stearate, 5.00% isopropyl myristate, 3.50% cetylethylhexanoate, 3.50% behenic acid Isocetyl, 3.00% oleyl erucate, 0.50% dimethicone, 5.00% deionized water, 0.50% triethanolamine (99%) and 1.00% propylene glycol, diazolidinini 9. A topical formulation according to claim 8 comprising lurea, methylparaben and propylparaben. A topical skin preparation for hormone replacement therapy comprising an effective skin penetration amount of one or more phosphate derivatives of estrogen and an acceptable carrier comprising :
The carrier comprises a complex of tocopheryl phosphate and a complexing agent, and the complexing agent comprises arginine, lysine, histazine, and the following formula:
NR ¹ R ² R ³
(Where
R ¹ is selected from the group comprising C6-C22 alkyl groups mixed with straight or branched chains and carbonyl derivatives thereof;
R ² and R ³ are independently H, CH ₂ COOX, CH ₂ CHOHCH ₂ SO ₃ X, CH ₂ CHOHCH ₂ OPO ₃ X, CH ₂ CH ₂ COOX, CH ₂ COOX, CH ₂ CH ₂ CHOHCH ₂ SO ₃ X or CH ₂ CH ₂ CHOHCH ₂ OPO ₃ X selected from the group consisting of H, Na, K, or alkanolamine when R ² and R ³ are not both H;
When R ¹ is RCO, R ² is CH ₃ and R ³ is (CH ₂ CH ₂ ) N (C ₂ H ₄ OH) —H ₂ CHOPO ₃ , or R ² and R ³ are taken together. Te _{N (CH 2) 2 N (} C 2 H 4 OH) is CH 2 COO-)
A topical skin preparation selected from the group consisting of: